Effect of thromboxane synthetase inhibitor on non-heart-beating donors in rat orthotopic liver transplantation.
BACKGROUND
The use of non-heart-beating donors could relieve donor organ shortage provided that the outcome of the recipients is not jeopardized.


METHODS
In this study we evaluated the effect of thromboxane synthetase inhibitor (OKY-046) on non-heart-beating donors in orthotopic liver transplantation in rodents. OKY-046 (OKY group, n = 8) or vehicle (control group, n = 8) was given to the donor animals for 60 minutes before the induction of 30 minutes of warm ischemia to the liver before transplantation and survival, and several parameters were compared between the two groups.


RESULTS
All recipients in the control group died within 2 days, whereas 67% of those of the OKY group had a 2-day survival and 44% had a 2-week survival (p < 0.01). Bile output from the allograft for 2 hours after reperfusion was significantly larger in the OKY group at all time points (p < 0.05). Furthermore, serum transaminase levels 10 minutes after reperfusion were significantly lower in the OKY group (p < 0.05), although those 120 minutes after reperfusion were comparable between the two groups. The thromboxane B2 level in liver tissue 10 and 120 minutes after reperfusion was significantly lower in the OKY group compared with the control group (p < 0.02 and p < 0.05, respectively).


CONCLUSIONS
These results indicate that OKY-046 given to the donor before the induction of warm ischemia could ameliorate ischemia/reperfusion injury of the hepatic allograft by reducing thromboxane A2 production after reperfusion.
Soejima
Y
Y
Department of Surgery II, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Yanaga
K
K
Nisizaki
T
T
Yoshizumi
T
T
Uchiyama
H
H
Sugimachi
K
K
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D001646:Bile / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006085:Graft Survival / Q000187:drug effects*; D006323:Heart Arrest; D007511:Ischemia; D016031:Liver Transplantation / Q000379:methods / Q000502:physiology*; D008297:Male; D008689:Methacrylates / Q000494:pharmacology*; D009926:Organ Preservation; D051381:Rats; D011917:Rats, Inbred Lew; D015424:Reperfusion; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors*; D013997:Time Factors; D014019:Tissue Donors; D014185:Transplantation, Isogeneic
D004791:Enzyme Inhibitors; D008689:Methacrylates; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D013930:Thromboxane-A Synthase; C034364:ozagrel